Uso de la nimodipina (Nimotop) en psicogeriatría / Use of the nimodipine (Nimotop) in psychogeriatric

La nimodipina (Nimotop) es una droga prometedora para el anciano demente y para pacientes no dementes. Varios estudios doble ciego han demostrado que la droga puede ser efectiva para los déficit cognitivos, rendimiento, afectividad e integración social. Las conclusiones derivadas de los resultados de varios experimentos sobre conducta en animales son significativos para predecir los efectos clínicos de la nimodipina (Nimotop)

Blood pressure and heart rate during treatment with nimodipine in patients with subarachnoid hemorrhage.

Careful observation of blood pressure and heart rate in patients with subarachnoid hemorrhage during therapy with nimodipine showed that blood pressure decreases mainly in hypertensive patients during the first hours of therapy or when treatment is started immediately with 2 mg per hour instead of the recommended initial dose of 1 mg per hour. Predominantly mild or moderate reversible falls in blood pressure were reported as side effects in 21/421 patients (5%). Electrocardiographic abnormalities such as tachycardia, bradycardia, arrhythmia or extrasystoles were reported as side effects during treatment with nimodipine in 18 patients (4,3%). Since the association of ECG abnormalities with subarachnoid hemorrhage has been known for many years it is likely that these abnormalities are not typical side effects of nimodipine but belong to the natural course of the disease.

Prevention of malignant hypertension in salt loaded "S" Dahl rats with the calcium antagonist nifedipine.

Female "S" Dahl rats, fed an 8% NaCl diet from the 6th week of age developed malignant hypertension and heart hypertrophy in the course of 6 weeks on the salt regimen. Simultaneous treatment with nifedipine (300 ppm in diet additional to 8% NaCl) prevented the increase in blood pressure, reduced heart hypertrophy and mortality and improved the impaired renal function in "S" rats. The decrease in hematocrit in salt loaded "S" rats was prevented by nifedipine. The prophylactic effect of the calcium antagonist nifedipine is only partly due to the prevention of increase in systemic vascular resistance. In addition an improvement of failed intrarenal hemodynamics by nifedipine can be postulated. This enables the kidney of "S" rats to excrete the salt load without increasing blood pressure and plasma volume.

Comparison of the effects of muzolimine and furosemide in patients with end-stage renal failure on chronic dialysis.

The pharmacodynamic effects of muzolimine and furosemide were compared in a single dose cross-over study in 8 patients on regular dialysis treatment, who had a residual diuresis of more than 300 ml/day. The study periods comprised two dialysis-free intervals of 3 days. On the second dialysis-free day either muzolimine 240 mg or furosemide 240 mg was administered orally. Urine was collected in 12-h periods on the pre-treatment, treatment and post-treatment days, and the excretion of sodium, potassium, urea and creatinine were measured. After administration of muzolimine 240 mg urine volume rose to twice that of the previous day, and sodium excretion increased approximately threefold. In contrast, the effect of furosemide 240 mg was not a pronounced; the diuresis was only 1.6 times that on the previous day and natriuresis was only 2.2 times as large. Excretion of potassium and creatinine was only slightly increased by either substance. The elimination of urea was increased by both substances to the same degree as the corresponding increase in diuresis.

[Pharmacodynamic and pharmacokinetic studies of muzolimine in patients with hepatogeneous ascites (author's transl)]. / Klinisch-pharmakologische und pharmakokinetische Untersuchungen zur Wirkung von Muzolimin bei Patienten mit hepatogenem Aszites.

A clinical pharmacological study was carried out with 11 patients suffering from hepatogeneous ascites. After pretreatment with spironolactone (twice daily 100 mg), 80 mg of a new loop diuretic, muzolimine, were administered orally in addition to 100 mg of spironolactone. The diuretic effect started rapidly, reached its maximum about 6 h after administration and declined slowly until 24 h. The electrolyte profile showed a pronounced excretion of sodium and chloride, whereas potassium excretion was distinctly lower. Sodium/potassium ratio was 5.9 during the first 8 hours, and the mean ratio was 5.2 during 24 hours. Urinary volume and sodium excretion were significantly correlated with plasma levels of muzolimine. Mean plasma half-life of muzolimine in these patients with liver cirrhosis was 7.9 h and was thus longer than in healthy volunteers.

Effect of praziquantel on clinical-chemical parameters in healthy and schistosome-infected mice.

The response of hepatic and haemotopoetic functions to treatment with praziquantel was studied using healthy and schistosome-infected mice. Female CF1 mice harbouring an 18 week old infection with Schistosoma mansoni and healthy uninfected mice of the same age were orally treated with 1 x 250 mg praziquantel/kg. The respective uninfected controls received the vehicle only. Blood samples were taken one, five, 14 and 28 days after treatment. Parameters studied were: activity of GOT, GPT and AP, concentration of glucose, blood clotting time, haemoglobin content, erythrocyte and leucocyte counts, PCV and body weight. The data were analyzed to reveal the effect of the three independent variables involved: infection, treatment and time after treatment. Infection of mice with S. mansoni for 18 weeks resulted in a depression of body weight, in a decrease of plasma GOT activity and of PCV and in increases of plasma GPT and AP activities, leucocyte counts and clotting time. Plasma glucose concentrations remained unaffected. The effects of treament with praziquantel were confined to the infected group. Changes attributable to the variable time were also more pronounced or even restricted to the infected treated group. Treatment of infected mice with praziquantel resulted in a temporary elevation of plasma GOT and GPT activities on Day 1 after treatment. Values had returned to normal on Day 5. Treatment further resulted in a slight but prolonged elevation of AP activities, a high leucocyte count on Day 5 after treatment and a normalization of the underweight and anaemic state of the infected mice. The nature of the effects observed after treatment with praziquantel is discussed in the light of corresponding data on the effect of treatment with hycanthone and SQ 18.506 in schistosome infected mice and Mastomys. It is concluded that the changes observed can be regarded as secondary, reflecting host responses to damaged parasites and healing processes.

Effects of a new diuretic on cerebrospinal fluid pressure in patients with supratentorial tumors.

The effect of a new, powerful diuretic on biochemical parameters, urine output, central venous pressure, blood pressure, and cerebrospinal fluid pressure in patients with supratentorial intracerebral tumors who showed signs and symptoms of increased intracranial pressure was tested. When compared to an untreated control group and to the steady-state data of each patient, CSF pressure was significantly reduced using a dose of 240 mg of the diuretic. The 120 mg dosage did not produce significant results. Normalization of increased cerebrospinal fluid pressure was not completely obtained using either dose. Used alone, this substance is not suitable for treatment of increased intracranial pressure due to brain edema in patients with intra-cerebral tumors. It might, however, be useful in combination with other medications.

Comparison of the pharmacodynamic effects of furosemide and BAY g 2821 and correlation of the pharmacodynamics and pharmacokinetics of BAY g 2821 (muzolimine).

In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first gwo hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.

[Comparative study on the saluretic activity of etacrynic acid and BAY g 2821 in patients with cardiac decompensation (author's transl)]. / Saluretischer Wirkungsvergleich von Etacrynsäure mit BAY g 2821 bei Patienten mit kardialer Dekompensation.

In a randomised double-blind comparative study 40 mg 3-amino-1-(3,4-dichloro-alpha-methyl-benzyl)-2-pyrazolin-5-one (BAY g 2821), a novel diuretic agent, were tested against 50 mg etacrynic acid in patients with cardiac decompensation. BAY g 2821 has a rapid onset of action which slowly decreases until 12 h after administration. Within a period between the second and the fourth hour after administration, the efficacy of BAY g 2821 is superior to that of etacrynic acid. The difference is statistically significant. The total elimination of BAY g 2821 is markedly more pronounced than that of etacrynic acid throughout the 5-day treatment course. Neither subjective nor objective side effects were observed.

The diuretic effect of muzolimine (Bay g 2821) on hepatogenic ascites.

A double-blind study was carried out in 22 patients with hepatogenic ascites to examine the effectiveness of the combination of muzolimine and spironolactone in comparison with combinations of furosemide and spironolactone and placebo and spironolactone. Despite the heterogeneous and variable case material, there was no significant difference between the 3 patient groups prior to treatment. After a diuretic-free preliminary period, all patients received 300 mg spironolactone daily plus 80 mg muzolimine, 80 mg furosemide or placebo for 7 days. Before the start of treatment and at daily intervals, measurements were made of waist size, body weight, and urinary and electrolyte elimination. Blood chemistry was investigated before treatment and on Days 4 and 7. Analysis of the results showed that the combination of muzolimine and spironolactone produced a statistiscally significant stronger saluretic effects than the other two combinations. This can be explained by the different sites of action of muzolimine and spironolactone, resulting in an additive effect. Neither subjective nor objective side-effects were observed during the 7-day treatment period.